Prof Aids Quest for Possible Alzheimer’s Treatments
Partnership Seeks Ways to Develop Therapeutic Uses for Promising Compounds
Researchers at UT Dallas and Southern Methodist University have partnered with a private company to develop potentially groundbreaking treatments for neurodegenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s.
Dr. Santosh D’Mello, professor of molecular and cell biology at UT Dallas, and Dr. Ed Biehl, professor of chemistry at SMU, published their findings in a recent issue of the Journal of Neuroscience Research showing that a family of novel small molecules proved effective in reducing neuronal loss in tissue culture and animal models of neurodegenerative disease.
Neurodegenerative diseases afflict millions of American costing the U.S. economy hundreds of millions of dollars annually. There are no effective cures for these brain diseases.
“The protective effect they display in tissue culture and animal models of neurodegenerative disease provide strong evidence of their promise as drugs to treat progressive and fatal human neurodegenerative diseases,” D’Mello said.
By partnering with the Dallas-based startup company EncephRx Inc., D’Mello and his colleagues hope to hasten clinical trials and devise human therapies using these compounds. Under an agreement with SMU, the UT Dallas Office of Technology Commercialization negotiated an exclusive license with the company for the jointly-owned compounds as a result of an inquiry from FirstStage BioVentures, parent company of EncephRx.
The family of compounds, called benzoxazines, was tested first in neurons cultured from rodent brains and induced to degenerate in tissue culture dishes by blocking neuronal activity. During this process, researchers noted a specific compound identified as HSB-13 proved protective against cellular degeneration. The compounds were synthesized in Biehl’s laboratory.
D’Mello’s team previously tested similar compounds, but found they had toxic effects at high concentrations. By further isolating structures within those compounds, they identified small molecules that protected nerve cells against damage and showed no measurable toxicity, even at higher doses.
Researchers also tested HSB-13 for potential use in treating Huntington’s Disease, a genetic illness causing progressive, irreversible brain damage. The compound was used in an animal model for Huntington’s and showed reduced loss of brain cells and improved behavioral performance. In collaboration with Dr. Doris Kretzschmar from the Oregon Health and Science University, Dr. D’Mello and his team also applied the compound in a fruit fly model for Alzheimer’s disease and observed that flies receiving HSB-13 lived longer than those that did not.
“These are very promising, early signs of therapeutic potential in people. Obviously, additional research needs to be done, but these compounds have the potential of slowing or stopping the relentless loss of brain cells in diseases such as Alzheimer’s and Parkinson’s disease,” D’Mello said.
“Obviously, additional research needs to be done, but these compounds have the potential of slowing or stopping the relentless loss of brain cells in diseases such as Alzheimer’s and Parkinson’s disease,” said Dr. Santosh D’Mello.
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